“Maximum tolerated dose” vs “fixed low‐dose” hydroxyurea for treatment of adults with sickle cell anemia

Abstract

Despite evidence that hydroxyurea is effective for sickle cell anemia (SCA), implementation of the "maximum tolerated dose" regimen in adults is poor. 1 We recently reported a study of "fixed low-dose" hydroxyurea (500 mg/day) for adults with SCA in Ibadan, Nigeria. 2 Here we compare the outcomes of "fixed low-dose" hydroxyurea in Nigeria with "maximum tolerated dose" hydroxyurea in the United States and Canada as reported in the Multicenter Study of Hydroxyurea (MSH). 3,4 The MSH was the seminal trial conducted in the 1990s that led to FDA approval of hydroxyurea for SCA. Responses to "fixed low-dose" and "maximum tolerated dose" hydroxyurea appear to be similar. We propose that these two regimens be compared in a prospective trial in adults with SCA. Hydroxyurea for SCA increases hemoglobin F and reduces pain crises, acute chest syndrome and blood transfusions. 5 The agent is initiated at 15 mg/kg/day in adults followed by dose escalations up to 35 mg/kg/day if tolerated-the "maximum tolerated dose" approach of

Hydroxycarbamide exposure and ovarian reserve in women with sickle cell disease in the Multicenter Study of Hydroxycarbamide

“…9 The presence of normal AMH in two small, HC-na€ ıve populations with sickle cell anaemia suggests that the disease alone may not reduce ovarian reserve in young women. Further clarification of the effects of HC on ovarian reserve will be especially important for the emerging generation of young adults who started HC in infancy or early childhood, 33,34 for girls and women treated in sub-Saharan Africa where both fixed-dose and maximally tolerated dose treatment strategies are under investigation, 35 and in women pursuing fertility preservation interventions before HSCT or gene therapy. 10,11 Fig 1 . Explanation of study population and sample availability.…”

Transcranial Doppler screening in Nigerian children with sickle cell disease: A 10‐year longitudinal study on the SPPIBA cohort

“…The 2020 American Society of Hematology guidelines 19 recommend the use of TCD screening and HU for primary stroke prevention in children with HbSS and HbSB 0 thalassaemia living in low‐ and middle‐income settings. A few clinical trials have shown the feasibility and safety of HU in different countries across Africa using different HU regimen; fixed dose and dose‐escalation regimen 18,20–23 …”

Design of an adaptive randomized clinical trial of intravenous citrulline for sickle cell pain crisis in the emergency department

“…This is partly because the clinical endpoints were different between the different phases of the trials [ 18 ]. In addition, the landmark phase 3 trial of hydroxyurea for the prevention of pain in SCD showed that hydroxyurea at maximum tolerated dose significantly decreases the frequency of pain crises although debate on use of low dose use hydroxurea with reduced toxicity led to further confirmatory trials [ 19 , 20 ]. The history of unsuccessful trials could complicate the challenging economics associated with funding studies for diseases with limited market value [ 21 ].…”